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Arsenic trioxide-mediated oxidative stress and genotoxicity in human hepatocellular carcinoma cells

Authors Alarifi S, Ali D, Alkahtani S, Siddiqui M, Ali BA

Received 17 September 2012

Accepted for publication 20 November 2012

Published 7 February 2013 Volume 2013:6 Pages 75—84

DOI https://doi.org/10.2147/OTT.S38227

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 4


Saud Alarifi,1 Daoud Ali,1 Saad Alkahtani,1 Maqsood A Siddiqui,2 Bahy A Ali2,3

1Cell and Molecular Laboratory, Department of Zoology, Faculty of Science, King Saud University, Riyadh, Saudi Arabia; 2DNA Research Chair, Department of Zoology, Faculty of Science, King Saud University, Riyadh, Saudi Arabia; 3Genetic Engineering & Biotechnology Research Institute City for Scientific Research and Technology Applications, Alexandria, Egypt

Background: Arsenic is a ubiquitous environmental toxicant, and abnormalities of the skin, lung, kidney, and liver are the most common outcomes of long-term arsenic exposure. This study was designed to investigate the possible mechanisms of genotoxicity induced by arsenic trioxide in human hepatocellular carcinoma cells.
Methods and results: A mild cytotoxic response of arsenic trioxide was observed in human hepatocellular carcinoma cells, as evident by (3-(4,5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) and lactate dehydrogenase assays after 24 and 48 hours of exposure. Arsenic trioxide elicited a significant (P < 0.01) reduction in glutathione (15.67% and 26.52%), with a concomitant increase in malondialdehyde level (67.80% and 72.25%; P < 0.01), superoxide dismutase (76.42% and 81.09%; P < 0.01), catalase (73.33% and 76.47%; P < 0.01), and reactive oxygen species generation (44.04% and 56.14%; P < 0.01) after 24 and 48 hours of exposure, respectively. Statistically significant (P < 0.01) induction of DNA damage was observed by the comet assay in cells exposed to arsenic trioxide. It was also observed that apoptosis occurred through activation of caspase-3 and phosphatidylserine externalization in human hepatocellular carcinoma cells exposed to arsenic trioxide.
Conclusion: The results demonstrate that arsenic trioxide induces apoptosis and genotoxicity in human hepatocellular carcinoma cells through reactive oxygen species and oxidative stress.

Keywords: arsenic trioxide, DNA damage, hepatocellular carcinoma cells, oxidative stress, apoptosis

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